Characteristics and outcome of ANCA-associated vasculitides induced by anti-thyroid drugs: a multicentre retrospective case-control study.

OBJECTIVE: Data on ANCA-associated vasculitis (AAV) induced by anti-thyroid drugs (ATD) are scarce. We aimed to describe the characteristics and outcome of these patients in comparison to primary AAV. METHODS: We performed a retrospective multicentre study including patients with ATD-induced AAV. We focused on ATD-induced microscopic polyangiitis (MPA) and compared them with primary MPA by matching each case with four controls by gender and year of diagnosis. RESULTS: Forty-five patients with ATD-induced AAV of whom 24 MPA were included. ANCA were positive in 44 patients (98%), including myeloperoxidase (MPO)-ANCA in 21 (47%), proteinase 3 (PR3)-ANCA in six (13%), and double positive MPO- and PR3-ANCA in 15 (33%). Main clinical manifestations were skin involvement (64%), arthralgia (51%) and glomerulonephritis (20%). ATD was discontinued in 98% of cases, allowing vasculitis remission in seven (16%). All the remaining patients achieved remission after glucocorticoids, in combination with rituximab in 11 (30%) or cyclophosphamide in four (11%). ATD were reintroduced in seven cases (16%) without any subsequent relapse. Compared with 96 matched primary MPA, ATD-induced MPA were younger at diagnosis (48 vs 65 years, P < 0.001), had more frequent cutaneous involvement (54 vs 25%, P = 0.007), but less frequent kidney (38 vs 73%, P = 0.02), and a lower risk of relapse (adjusted HR 0.07; 95% CI 0.01, 0.65, P = 0.019). CONCLUSION: ATD-induced AAV were mainly MPA with MPO-ANCA, but double MPO- and PR3-ANCA positivity was frequent. The most common manifestations were skin and musculoskeletal manifestations. ATD-induced MPA were less severe and showed a lower risk of relapse than primary MPA.

Montelukast as a Rescue and Premedication for Rituximab Infusion Reactions.

Rituximab (RTX) is a monoclonal antibody often used in patient treatment of malignancies and several rheumatological disorders, including vasculitides.1-3 It has become an essential component of many treatment protocols; however, is commonly associated with hypersensitivity infusion reactions.1.

Systemic lupus erythematosus presenting with atypical hemolytic uremic syndrome: a case report and review of the literature.

Systemic lupus erythematosus (SLE) can present with a diverse array of hematologic manifestations, among which atypical hemolytic uremic syndrome (aHUS) is a rare entity. SLE-triggered aHUS has significant morbidity and mortality without timely intervention, yet its frequency remains uncertain and optimal strategies for complement-directed therapies are largely expert-driven. We performed a comprehensive literature review and present a case of a 23-year-old female newly diagnosed with SLE/class IV lupus nephritis who developed aHUS that rapidly responded to the C5 antagonist, eculizumab. Review of the current literature identified forty-nine published cases of SLE with concurrent aHUS and revealed a predilection for aHUS in younger SLE patients, concurrent presentation with lupus nephritis, anti-dsDNA positivity, and complement system abnormalities. Over seventy percent of cases used eculizumab as complement-directed therapy with a trend towards faster time to improvement in laboratory parameters, though reported outcomes were highly variable. Early recognition of aHUS in SLE is pivotal in guiding appropriate therapeutic interventions, and prompt initiation of eculizumab may reduce the potential morbidity associated with plasmapheresis and additional immunosuppression. While eculizumab showcases promising results, its optimal timing and duration remain elusive. An understanding of a patients' complement genetics could aid management strategies, and ongoing research into complement-targeted therapies offers promising avenues for both SLE and aHUS treatment.

CanVasc consensus recommendations for the use of avacopan in antineutrophil cytoplasm antibody-associated vasculitis: 2022 addendum.

OBJECTIVE: In 2020, the Canadian Vasculitis Research Network (CanVasc) published their updated recommendations for the management of ANCA-associated vasculitides (AAV). The current addendum provides further recommendations regarding the use of avacopan in AAV based on a review of newly available evidence. METHODS: An updated systematic literature review on avacopan (formerly, CCX168) using Medline, Embase, and the Cochrane Library was performed for publications up to September 2022. New recommendations were developed and categorized according to the EULAR grading levels, as done for previous CanVasc recommendations. A modified Delphi procedure and videoconferences were used to reach ≥80% consensus on the inclusion, wording and grading of each recommendation. RESULTS: Three new recommendations were developed. They focus on avacopan therapy indication and duration, as well as timely glucocorticoid tapering. CONCLUSION: These 2022 addended recommendations provide rheumatologists, nephrologists and other specialists caring for patients with AAV with guidance for the use of avacopan, based on current evidence and consensus from Canadian experts.

Skin disorders and interstitial lung disease: Part I-Screening, diagnosis, and therapeutic principles.

Numerous inflammatory, neoplastic, and genetic skin disorders are associated with interstitial lung disease (ILD), the fibrosing inflammation of lung parenchyma that has significant morbidity and mortality. Therefore, the dermatologist plays a major role in the early detection and appropriate referral of patients at risk for ILD. Part 1 of this 2-part CME outlines the pathophysiology of ILD and focuses on clinical screening and therapeutic principles applicable to dermatological patients who are at risk for ILD. Patients with clinical symptoms of ILD should be screened with pulmonary function tests and high-resolution chest computed tomography. Screening for pulmonary hypertension should be considered in high-risk patients. Early identification and elimination of pulmonary risk factors, including smoking and gastroesophageal reflux disease, are essential in improving respiratory outcomes. First-line treatment interventions for ILD in a dermatological setting include mycophenolate mofetil, but the choice of therapeutic agents depends on the nature of the primary disease, the severity of ILD, and comorbidities and should be the result of a multidisciplinary assessment. Better awareness of ILD among medical dermatologists and close interdisciplinary collaborations are likely to prevent treatment delays improving long-term outcomes.

Skin disorders and interstitial lung disease: Part II-The spectrum of cutaneous diseases with lung disease association.

Part 2 of this 2-part CME introduces dermatologists to noninfectious inflammatory skin diseases associated with pulmonary involvement. In many cases, dermatologists may be the first physicians recognizing respiratory complications associated with these diagnoses. Because pulmonary involvement is often the leading cause of morbidity and mortality, dermatologists should be comfortable screening and monitoring for lung disease in high-risk patients, recognizing cutaneous stigmata of lung disease in these patients and referring to pulmonary specialists, when appropriate, for prompt treatment initiation. Some treatments used for skin disease may not be appropriate in the context of lung disease and hence, choosing a holistic approach is important. Interstitial lung disease and pulmonary hypertension are the most common pulmonary complications and a significant cause of mortality in autoimmune connective tissue diseases, especially systemic sclerosis, dermatomyositis, and mixed connective tissue disease. Pulmonary complications, notably interstitial lung disease, are also common and life-threatening in sarcoidosis and vasculitis, while they are variable in neutrophilic and autoimmune blistering diseases.

Metabolomic profile overlap in prototypical autoimmune humoral disease: a comparison of myasthenia gravis and rheumatoid arthritis.

INTRODUCTION: Myasthenia gravis (MG) and rheumatoid arthritis (RA) are examples of antibody-mediated chronic, progressive autoimmune diseases. Phenotypically dissimilar, MG and RA share common immunological features. However, the immunometabolomic features common to humoral autoimmune diseases remain largely unexplored. OBJECTIVES: The aim of this study was to reveal and illustrate the metabolomic profile overlap found between these two diseases and describe the immunometabolomic significance. METHODS: Metabolic analyses using acid- and dansyl-labelled was performed on serum from adult patients with seropositive MG (n = 46), RA (n = 23) and healthy controls (n = 49) presenting to the University of Alberta Hospital specialty clinics. Chemical isotope labelling liquid chromatography mass spectrometry (CIL LC-MS) methods were utilized to assess the serum metabolome in patients; 12C/13C-dansyl chloride (DnsCl) was used to label amine/phenol metabolites and 12C/13C-p-dimethylaminophenacyl bromide (DmPA) was used for carboxylic acids. Metabolites matching our criteria for significance were selected if they were present in both groups. Multivariate statistical analysis [including principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA)] and biochemical pathway analysis was then conducted to gain understanding of the principal pathways involved in antibody-mediated pathogenesis. RESULTS: We found 20 metabolites dysregulated in both MG and RA when compared to healthy controls. Most prominently, observed changes were related to pathways associated with phenylalanine metabolism, tyrosine metabolism, ubiquinone and other terpenoid-quinone biosynthesis, and pyruvate metabolism. CONCLUSION: From these results it is evident that many metabolites are common to humoral disease and exhibit significant immunometabolomic properties. This observation may lead to an enhanced understanding of the metabolic underpinnings common to antibody-mediated autoimmune disease. Further, contextualizing these findings within a larger clinical and systems biology context could provide new insights into the pathogenesis and management of these diseases.

Human pegivirus-1 associated leukoencephalitis: Clinical and molecular features.

Etiologic diagnosis is uncertain in 35% to 50% of patients with encephalitis, despite its substantial global prevalence and disease burden. We report on 2 adult female patients with fatal leukoencephalitis associated with human pegivirus-1 (HPgV-1) brain infection. Neuroimaging showed inflammatory changes in cerebral white matter. Brain-derived HPgV-1 RNA sequences clustered phylogenetically with other pegiviruses despite an 87-nucleotide deletion in the viral nonstructural (NS)2 gene. Neuropathology disclosed lymphocyte infiltration and gliosis predominantly in brain white matter. HPgV-1 NS5A antigen was detected in lymphocytes as well as in astrocytes and oligodendrocytes. HPgV-1 neuroadaptation should be considered in the differential diagnosis of progressive leukoencephalitis in humans. Ann Neurol 2018;84:789-795.

Planning for the Rheumatologist Workforce: Factors Associated With Work Hours and Volumes.

OBJECTIVE: The aim of this study was to evaluate factors associated with rheumatologists' clinical work hours and patient volumes based on a national workforce survey in rheumatology. METHODS: Adult rheumatologists who participated in a 2015 workforce survey were included (n = 255). Univariate analysis evaluated the relationship between demographics (sex, age, academic vs. community practice, billing fee for service vs. other plan, years in practice, retirement plans) and workload (total hours and number of ½-day clinics per week) or patient volumes (number of new and follow-up consults per week). Multiple linear regression models were used to evaluate the relationship between practice type, sex, age, and working hours or clinical volumes. RESULTS: Male rheumatologists had more ½-day clinics (p = 0.05) and saw more new patients per week (p = 0.001) compared with females. Community rheumatologists had more ½-day clinics and new and follow-up visits per week (all p < 0.01). Fee-for-service rheumatologists reported more ½-day clinics per week (p < 0.001) and follow-ups (p = 0.04). Workload did not vary by age, years in practice, or retirement plans. In multivariate analysis, community practice remained independently associated with higher patient volumes and more clinics per week. Female rheumatologists reported fewer clinics and fewer follow-up patients per week than males, but this did not affect the duration of working hours or new consultations. Age was not associated with work volumes or hours. CONCLUSIONS: Practice type and rheumatologist sex should be considered when evaluating rheumatologist workforce needs, as the proportion of female rheumatologists has increased over time and alternative billing practices have been introduced in many centers.

Conversion rates of abstracts presented at the Canadian Rheumatology Association Annual Meetings into full-text journal articles.

Dissemination of research studies is important for research ideas to be transformed from initial abstracts to full publications. Analyses of the scientific impact and publication record of the Canadian Rheumatology Association (CRA) Annual meeting have not been previously described. This study determines the publication rate of abstracts presented at the CRA Annual Meetings 2005-2013 to full-text journal articles and the factors associated with publication. Program records of previous CRA meetings from 2005 to 2013 were obtained. Abstracts were searched for corresponding full-text publication in Google Scholar and PubMed using a search algorithm. Abstracts and subsequent published articles were evaluated for type of abstract, time to publication, study type, publishing journal, and journal impact factor. A total of 1401 abstracts were included in the study, 567 of which were converted to full publications. The average time to publication was 19.7 months, with 89% of abstracts published within 3 years of being presented. Eighty-three percent of abstracts were clinical in nature, and 58% of published studies were observational in design. Articles were published in a wide range of journals, with the top publisher being the Journal of Rheumatology (31%). Average time to publication was 19.7 months. Eighty-six percent of articles had a Journal Impact Factor > 2. Overall, 40.5% of abstracts presented at the CRA Annual Meetings 2005-2013 were published. Further research is needed to determine barriers and reasons for abstracts not being published as full-text articles.

Microscopic Polyangiitis with Spinal Cord Involvement: A Case Report and Review of the Literature.

BACKGROUND: Microscopic polyangiitis (MPA) is an ANCA-associated vasculitis (AAV; ANCA denotes antineutrophil cytoplasmic antibody) that causes necrotizing inflammation of small blood vessels. Renal and pulmonary manifestations are common whereas central nervous system (CNS) involvement, and in particular spinal disease, is rare. METHODS: We reviewed a case of MPA presenting with spinal intradural hemorrhage and intracerebral hemorrhage. We also summarized all reported cases of AAV with spinal cord involvement in the literature (database search included MEDLINE, Embase, Scopus, and Proquest with no date or language restriction). RESULTS: We reviewed 20 cases of AAV with spinal cord involvement (12 granulomatosis with polyangiitis [GPA], 4 eosinophilic granulomatosis with polyangiitis, 2 MPA, and 2 cases diagnosed as AAV only) and reported demographic information, clinical features, methods of diagnosis, treatment, and patient outcome. Although CNS involvement has been associated with a poor prognosis, 14 of 18 cases that reported outcome data achieved remission during follow-up. Death occurred in 3 patients diagnosed with GPA and in 1 patient with MPA. Our patient with MPA deteriorated rapidly despite use of prednisone and died. CONCLUSIONS: AAV can present with brain and spinal cord involvement, even in the absence of systemic disease. CNS disease may be responsive to immunosuppressive therapy (e.g., steroids and cyclophosphamide) in several of the cases reviewed.

Tocilizumab for Treating Takayasu's Arteritis and Associated Stroke: A Case Series and Updated Review of the Literature.

BACKGROUND: Takayasu's arteritis (TA) is a rare inflammatory disease that can result in stroke. Treatment of patients with TA requires prolonged use of corticosteroids (CS). We assessed the effectiveness of tocilizumab (TCZ) in inducing disease remission and reducing CS doses in patients with TA. METHODS: We retrospectively reviewed all patients with TA treated with TCZ and determined their response to therapy and adverse effects. We also summarized all reported TA patients treated with TCZ in the literature (both PubMed and MEDLINE) with no date or language restrictions and determined the utility of TCZ in inducing remission, acting as a CS sparing agent, and its adverse effects. RESULTS: TCZ induced remission and reduction of CS doses in all 3 cases of TA in our cohort. Remission was achieved in 2 patients where stroke was the initial manifestation of active TA. In total, 3 of 4 patients with TA and stroke (2 from our study and 2 from other studies) treated with TCZ achieved remission and stability of their disease. We also identified 30 patients with TA treated with TCZ in the literature, of which 76.7% achieved remission despite the lack of sustained remission with other biological agents. In addition, TCZ resulted in a statistically significant reduction of CS in patients on CS before using TCZ (median, -8.8 mg/day; interquartile range, -19.4, to -3.4 mg/day; Wilcoxon P value, .0002). CONCLUSIONS: TCZ is a promising alternative for treating TA refractory to other biologics and for TA patients with stroke.

Development and evaluation of shared decision-making tools in rheumatology: A scoping review.

INTRODUCTION: Shared decision-making (SDM) tools are facilitators of decision-making through a collaborative process between patients/caregivers and clinicians. These tools help clinicians understand patient's perspectives and help patients in making informed decisions based on their preferences. Despite their usefulness for both patients and clinicians, SDM tools are not widely implemented in everyday practice. One barrier is the lack of clarity on the development and evaluation processes of these tools. Such processes have not been previously described in the field of rheumatology. OBJECTIVE: To describe the development and evaluation processes of shared decision-making (SDM) tools used in rheumatology. METHODS: Bibliographic databases (e.g., EMBASE and CINAHL) were searched for relevant articles. Guidelines for the PRISMA extension for scoping reviews were followed. Studies included were: addressing SDM among adults in rheumatology, focusing on development and/or evaluation of SDM tool, full texts, empirical research, and in the English language. RESULTS: Of the 2030 records screened, forty-six reports addressing 36 SDM tools were included. Development basis and evaluation measures varied across the studies. The most commonly reported development basis was the International Patient Decision Aids Standards (IPDAS) criteria (19/36, 53 %). Other developmental foundations reported were: The Ottawa Decision Support Framework (ODSF) (6/36, 16 %), Informed Medical Decision Foundation elements (3/36, 8 %), edutainment principles (2/36, 5.5 %), and others (e.g. DISCERN and MARKOV Model) (9/31,29 %). The most commonly used evaluation measures were the Decisional Conflict Scale (18/46, 39 %), acceptability and knowledge (7/46, 15 %), and the preparation for decision-making scale (5/46,11 %). CONCLUSION: For better quality and wider implementation of such tools, there is a need for detailed, transparent, systematic, and consistent reporting of development methods and evaluation measures. Using established checklists for reporting development and evaluation is encouraged.

Evidence for the use of cannabis-based medicines in osteoarthritis: a scoping review.

The purpose of this study was to conduct a scoping review to describe the evidence on the efficacy and safety of using cannabis-based medicines for osteoarthritis. The review was conducted following the framework proposed by Arksey and O'Malley and reported following PRISMA extension for scoping reviews guidelines. We conducted a comprehensive search across various databases including MEDLINE, Embase, Cochrane Library, CINAHL, Scopus, and Proquest, spanning from inception of each database to March 2023. We retrieved 2533 citations, and after deduplication, title and abstract screening, and full-text screening, 10 articles were included for analysis. These studies were composed of randomized-controlled trials (n = 4/10), cross-sectional surveys (n = 3/10), case studies (n = 2/10), and a cohort study (n = 1/10). Evidence for using cannabis-based medicines was mixed, with just 60% (n = 6/10) of included studies reporting statistically significant improvements in pain. Studies with larger samples sizes and longer durations of exposure did not find significant benefits for pain. The few adverse effects reported were generally mild and affected a minority of participants. Several studies also discovered that cannabis-based medicines were associated with a reduction in opioid use. Currently available data on the use of cannabis-based medicines in osteoarthritis is insufficient to make recommendations. Future research should address concerns regarding small sample sizes and short treatment durations to provide a more robust evidence base. Key Points • Current evidence remains mixed; studies that found a positive benefit with using cannabis-based medicines had limitations with small sample sizes and short durations of exposure • The use of cannabis-based medicines in osteoarthritis appears to be generally well tolerated, adverse effects are mild and experienced by a minority of participants • Cannabis-based medicines may decrease the use of opioids in patients with osteoarthritis • Future research should address the gaps in long-term efficacy and safety data.

Incidental findings on FDG-PET/CT in large vessel vasculitis.

This study aims to determine the number and type of incidental findings detected on positron emission tomography (PET)/CT in a cohort of patients with large vessel vasculitis (LVV). Reports from PET/CT studies along with the medical charts of a cohort of patients with LVV from a Rheumatology clinic in Edmonton, Alberta, Canada, were retrospectively reviewed. Incidental findings from PET/CT, along with follow-up studies and their diagnosis were documented. The data was analyzed with descriptive statistics. The disease activity of 40 patients, with an average age of 65.8 years, was investigated using PET/CT. A statistically significant increase in incidental findings with age was observed. A total of 61 incidental findings were found in 26 (65%) patients. Of these findings, 25 were in the abdomen and pelvis. The most common incidental finding was lymphadenopathy. Follow-up investigations of incidental findings lead to 5 clinically significant findings including metastatic adenocarcinoma, Mycobacterium avium infection, papillary thyroid carcinoma, pheochromocytoma, and stroke. PET/CT is a reliable tool for determining disease activity in LVV patients and the implications of incidental findings need to be discussed with patients by the ordering care provider. This study demonstrates that incidental findings on PET/CT scan are common and increase with age in patients with LVV. A significant number of patients required further investigation for incidental findings. Key Points • Incidental findings on PET/CT scan are common in our patient population with LVV. • Frequency of incidental findings in our patient population with LVV increased with age. • Findings from this study can be used by ordering providers to have an informed conversation with their patient about the frequency of incidental findings on PET/CT scans.

Thoughts and Experiences of Behçet Disease From Participants on a Reddit Subforum: Qualitative Online Community Analysis.

BACKGROUND: Behçet disease (BD) is a type of vasculitis with relapsing episodes and multisystemic clinical features, associated with significant morbidity and impact on patients' lives. People affected by BD often participate in discussions of their illness experiences. In-person support groups have limited physical accessibility and a relative lack of anonymity; however, online communities have become increasingly popular. OBJECTIVE: This study investigates the perspectives and experiences of people affected by BD by examining the content shared and discussed on a subforum of the website Reddit-a popular online space for anonymous discussions. METHODS: All discussion threads posted between March 9, 2021, and March 12, 2022, including posts and comments, were examined from the subforum "r/Behcets," an anonymous online community of 1100 members as of March 2022. A Grounded Theory analysis was completed to identify themes and subthemes, and notable quotes were extracted from the threads. Parameters extracted from each post included the number of comments, net upvotes, category, and subcategories. Two research team members read the posts separately to identify initial codes and themes to ensure data saturation was achieved. RESULTS: Six recurring themes were identified: (1) finding connectedness and perspectives through shared experiences, (2) struggles of the diagnostic odyssey, (3) sharing or inquiring about symptoms, (4) expressing strong emotions relating to the experience of BD, (5) the impact of BD on quality of life and personal relationships, as well as (6) COVID-19 and the COVID-19 vaccination in relation to BD. Subthemes within each theme were also identified and explored. CONCLUSIONS: This novel study provides a qualitative exploration of the perspectives and experiences of people affected by BD, shared in the anonymous and accessible online community of Reddit. The study found that people impacted by an illness seek to connect and receive validation through shared conditions and experiences. By examining the content shared in r/Behcets, this study highlights the needs of people affected by BD, identifying gaps and areas for improvement in the in-person support they receive.